EP0927719A1 - Dérivés de triazole et leurs sels, leurs procédés de préparation et compositions pharmaceutiques les contenant - Google Patents
Dérivés de triazole et leurs sels, leurs procédés de préparation et compositions pharmaceutiques les contenant Download PDFInfo
- Publication number
- EP0927719A1 EP0927719A1 EP98123589A EP98123589A EP0927719A1 EP 0927719 A1 EP0927719 A1 EP 0927719A1 EP 98123589 A EP98123589 A EP 98123589A EP 98123589 A EP98123589 A EP 98123589A EP 0927719 A1 EP0927719 A1 EP 0927719A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- difluoro
- ethylthio
- salt
- triazole
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/48—Compounds containing oxirane rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. ester or nitrile radicals
Definitions
- This invention relates to a triazole derivative or salt thereof which has excellent antimycotic action and high safety, an intermediate for preparing said compound and a pharmaceutical comprising said compound as an effective ingredient.
- Mycosis can be classified into two types, that is, superficial mycosis represented by various trichophytosis, marginated eczema, psoriasis, cutaneous candidiasis or the like and deep seated mycosis represented by mycotic meningitis, mycotic infectious disease of respiratory organ, fungemia, mycosis of urinary tract or the like.
- superficial mycosis represented by various trichophytosis, marginated eczema, psoriasis, cutaneous candidiasis or the like
- deep seated mycosis such as candidiasis or aspergillosis tends to show a marked increase in recent days owing to the frequent use of an anticancer chemotherapeutic agent or immunosuppressive agent or lowering in the bioimmunology due to HIV infection or the like.
- an anticancer chemotherapeutic agent or immunosuppressive agent or lowering in the bioimmunology due to HIV infection or the like.
- an object of the present invention is to provide a compound which has high safety and has antimycotic activity effective against Aspergillus spp. and Candida spp.
- the present inventors synthesized a number of triazole derivatives and salts thereof and carried out an investigation on their antimycotic activity effective against Aspergillus spp. and Candida spp.
- an ethylthio- or ethylsulfonyl-containing triazole derivative represented by the below-described formula (1) and a salt thereof are superior in antimycotic activity against fungi including Aspergillus spp. and Candida spp. and also in safety to the analogous compounds which have been known to date, leading to the completion of the present invention.
- a triazole derivative represented by the following formula (1): wherein R 1 represents a hydrogen atom, lower alkyl group or aralkyl group, X 1 and X 2 are the same or different and each independently represents a hydrogen atom, a halogen atom or a halogenoalkyl group, n stands for an integer of 0 to 2, or salt thereof; an intermediate for preparing said compound; and a preparation process of these compounds.
- a pharmaceutical comprising the triazole derivative (1) or salt thereof as an effective ingredient.
- a pharmaceutical composition comprising the triazole derivative (1) or salt thereof and a pharmacologically acceptable carrier.
- a treating method of mycotic infections which comprises administering to a patient the triazole derivative (1) or salt thereof.
- examples of the lower alkyl group represented by R 1 in the formula (1) include linear or branched C 1-6 alkyl groups. Specific examples include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl i-pentyl and n-hexyl.
- aralkyl group represented by R 1 C 7-10 aralkyl groups are preferred, with phenyl-C 1-4 alkyl groups being more preferred. Specific examples include benzyl and phenetyl and phenylpropyl.
- methyl and benzyl groups are preferred.
- the halogen atom represented by X 1 or X 2 include fluorine, chlorine, bromine and iodine atoms, with the fluorine and chlorine atoms being particularly preferred.
- the halogenoalkyl group include the above-exemplified C 1-6 alkyl groups substituted by the above-exemplified halogen atom. Among them, a perfluoroalkyl group is preferred, with trifluoromethyl and pentafluoroethyl groups being particularly preferred and trifluoromethyl group being more preferred.
- the number n of oxygen atoms stands for an integer of 0 to 2, with 0 and 2 being preferred.
- salt of the triazole derivative (1) of the present invention is a pharmacologically acceptable salt.
- examples include acid addition salts such as hydrochlorides, nitrates, hydrobromides, p-toluenesulfonates, methanesulfonates, fumarates, succinates and lactates.
- Compound (1a) that is, a compound of the formula (1) wherein n stands for 0 can be prepared by introducing an ethylthio group into a 2-halo-acetophenone derivative (5) which is a known compound, difluorinating the resulting ethylthio compound (4) into Compound (2) and directly introducing a triazole methyl group into Compound (2) or first introducing an epoxymethylene group into Compound (2) to obtain Compound (3) and then introducing a triazole group into Compound (3).
- the R 1 of the resulting Compound (1a) can be alkylated or aralkylated as desired.
- Compound (1a) By the oxidation of Compound (1a), Compound (1b), that is, a compound of the formula (1) wherein n stands for 1 or Compound (1c), that is, a compound of the formula (1) wherein n stands for 2 can be prepared. Alternatively, Compound (1c) can be prepared by the oxidation of Compound (1b).
- a 2,2-difluoro-2-ethylthioacetophenone derivative represented by the formula (2) and an oxirane derivative represented by the formula (3) are novel compounds synthesized by the present inventors and are useful as an intermediate for the synthesis of a triazole derivative (1).
- Compound (4) can be prepared by introducing an ethylthio group into Compound (5).
- Compound (4) can be prepared by reacting Compound (5) with ethyl mercaptan in the presence of a base.
- the reaction solvent include alcoholic solvents such as methanol and ethanol, N,N-dimethylformamide, 1,4-dioxane and tetrahydrofuran, with the alcoholic solvents, particularly, methanol being preferred.
- alcoholic solvents such as methanol and ethanol, N,N-dimethylformamide, 1,4-dioxane and tetrahydrofuran, with the alcoholic solvents, particularly, methanol being preferred.
- sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium methoxide, sodium ethoxide, pyridine, triethylamine or the like is usable. Among them, potassium carbonate is preferred.
- Compound (2) can be prepared by reacting Compound (4) with a fluorinating reagent in a solvent.
- fluorinating agent examples include fluorine gas, perchloryl fluoride, potassium fluoride, spray-dried potassium fluoride, freeze-dried potassium fluoride, tetraalkylammonium fluoride, tris(dimethylamino)sulfa(trimethylsilyl)difluoride, N-fluoropyridone, N-fluoro-N-alkyl-arenesulfonamide, N-fluoroquinuclidinium salt, N-fluoroperfluoroalkyl sulfonimide, N-fluorosaltum, fluorinated xenon, N-fluoropyridinium salt and N-fluoropyridinium sulfonate.
- Examples of the commercially available fluorinating reagent include "Onoda Fluorinates FP-T300, FP-T500, FP-T700, FP-B300, FP-B500, FP-B700 and FP-B800" (trade names; products of Chichibu Onoda Co., Ltd.) and "MEC-01, MEC-02, MEC-03, MEC-04 and MEC-05" (trade names; products of Daikin Industries, Ltd.). It is preferred to use the fluorinating reagent in an amount of 2 to 20 equivalents per mole of Compound (4).
- reaction solvent examples include 1,2-dichloroethane, 1,1,2-trichloroethane, chloroform, methylene chloride, diethyl ether, ethyl acetate and tetrahydrofuran. Among them, 1,1,2-trichloroethane is preferred.
- the reaction temperature is -78°C to the boiling point of a solvent, with 80 to 100°C being preferred.
- Direct synthesis from Compound (2) to Compound (1a) is carried out by reacting 1 mole of Compound (2) with 1 to 5 moles of an epoxymethylene-introducing agent and 1 to 4 moles of 1,2,4-triazole or alkaline metal salt thereof at -100°C to room temperature or boiling point of the solvent for 1 to 30 hours in a solvent.
- the epoxymethylene-introducing agent include trimethylsulfoxonium iodide and trimethyl-sulfonium iodide.
- the base include sodium hydroxide, potassium hydroxide, barium hydroxide, sodium methoxide, sodium carbonate, potassium carbonate and sodium hydride, with potassium hydroxide being particularly preferred.
- the solvent methanol, ethanol, isopropanol, n-butanol, sec-butanol, t-butanol and the like are preferred.
- Compound (1a) can be prepared via Compound (3).
- Compound (3) can be obtained by reacting Compound (2) with 1 to 2 equivalents of an epoxymethylene-introducing agent such as trimethylsulfoxonium iodide or trimethylsulfonium iodide in the presence of 1 to 5 equivalents of an alkali.
- Dimethylsulfoxide, tetrahydrofuran or the like can be suitably used as a solvent.
- the base include sodium hydroxide, potassium hydroxide, barium hydroxide, sodium methoxide, sodium ethoxide, sodium carbonate, potassium carbonate and sodium hydride, with sodium hydride and sodium methoxide being particularly preferred.
- the reaction temperature preferably ranges from -100°C to the boiling point of the solvent, with a range of from -40 to 50°C being particularly preferred.
- Compound (1a) containing as R 1 a hydrogen atom can be prepared by reacting Compound (3) with 1,2,4-triazole or alkali metal salt thereof in a solvent in the presence of a base.
- a solvent include N,N-dimethylformamide, acetonitrile, N,N-dimethylacetamide and dimethylsulfoxide.
- the base include sodium hydroxide, potassium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate and tert-butoxy potassium.
- the reaction temperature preferably ranges from 0°C to the boiling point of the solvent, with a range of 20 to 60°C being particularly preferred.
- the solvent examples include alcoholic solvents such as methanol and ethanol, nonaqueous polar solvents such as N,N-dimethylformamide (DMF) and ether solvents such as 2,4-dioxane and tetrahydrofuran (THF), with DMF being particularly preferred.
- alcoholic solvents such as methanol and ethanol
- nonaqueous polar solvents such as N,N-dimethylformamide (DMF)
- ether solvents such as 2,4-dioxane and tetrahydrofuran (THF)
- THF tetrahydrofuran
- the reaction temperature preferably ranges from -40°C to the boiling point of the solvent, with 0 to 20°C being particularly preferred.
- Compound (1c) can be prepared by adding at least 2 equivalents, preferably 2.2 to 2.3 equivalents of an oxidizing agent to Compound (1a).
- the oxidizing agent include m-chloroperbenzoic acid, aqueous hydrogen peroxide, peracetic acid, tetrapropylammonium perruthenate, osmium tetraoxide, potassium permanganate and oxone.
- the solvent include chloroform, dichloromethane, acetic acid, methanol, water, acetonitrile and carbon tetrachloride, and mixtures thereof.
- the reaction temperature is preferably -40°C to the boiling point of the solvent, with 0 to 50°C being particularly preferred.
- ruthenium trichloride, selenium dioxide, sodium tungstate, sodium molybdate and vanadium oxide may be used as a catalyst.
- Compound (1b) can be prepared by adding 1 to 2 equivalents, preferably 1.2 equivalents of an oxidizing agent to Compound (1a).
- the oxidizing agent include m-chloroperbenzoic acid, aqueous hydrogen peroxide, peracetic acid, tetrapropylammonium perruthenate, osmium tetraoxide, potassium permanganate and oxone.
- the solvent include chloroform, dichloromethane, acetic acid, methanol, water, acetonitrile and carbon tetrachloride, and mixtures thereof.
- the reaction temperature is preferably -40°C to the boiling point of the solvent, with 0 to 50°C being particularly preferred.
- ruthenium trichloride, selenium dioxide, sodium tungstate, sodium molybdate and vanadium oxide may be used as a catalyst.
- Step (1b-1c) can be carried out similarly.
- Compounds (1a), (1b) and (1c) each has enantiomers based on its asymmetric carbon atom.
- Such an optically active substance can be prepared by separating using a column for separation of an optical isomer.
- the optically active stationary phase include synthetic optically active polymers, natural high molecules and amino acid metal complexes. Among them, a cellulose-derivative-coated silica gel is preferred.
- commercially-available products such as CHIRALCEL OD and CHIRALPAK AS (each, trade name; product of Daicel Chemical Industries, Ltd.) can be used, with CHIRALCEL OD being particularly preferred.
- chromatography liquid chromatography is preferred. In this case, hexane - ethanol, hexane - isopropyl alcohol can be used as an eluent as a mobile phase.
- the optically active substance can also be prepared by optical resolution.
- the reagent for optical resolution include optically active camphor-sulfonic acid or salt thereof which may be substituted with a halogen atom. Specific examples include (+)-camphor-10-sulfonic acid, (-)-camphor-10-sulfonic acid, (+)-3-bromocamphor-8-sulfonic acid, (-)-3-bromocamphor-8-sulfonic acid, (+)-3-bromocamphor-10-sulfonic acid, (-)-3-bromocamphor-10-sulfonic acid, ammonium (+)-3-bromocamphor-8-sulfonate and ammonium (-)-3-bromocamphor-7-sulfonate.
- (+)-3-bromocamphor-8-sulfonic acid, (-)-3-bromocamphor-8-sulfonic acid, ammonium (+)-3-bromocamphor-8-sulfonate and ammonium (-)-3-bromocamphor-7-sulfonate are particularly preferred.
- the target product can be isolated, for example, by recrystallization, various types of chromatography or the like.
- the target compound can be converted into a desired salt in a conventional manner.
- a pharmaceutical particularly, an antimycotic can be obtained in various dosage forms such as tablets, granules, powders, capsules, suspensions, injections, suppositories and external preparations.
- a pharmaceutical by incorporating therein a pharmacologically acceptable carrier.
- a solid preparation can be prepared in a conventional manner by adding to the invention compound (1) an excipient and, if necessary, a binder, disintegrator, extender, coating agent, sugar-coating agent and/or the like.
- An injection may be prepared by dissolving, dispersing or emulsifying the invention compound (1) in an aqueous carrier such as distilled water for injection to form an injection liquid in advance or to prepare powder for injection and dissolve it upon use.
- an aqueous carrier such as distilled water for injection
- Examples of the administration method of the injection include intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration and instillation.
- the dose of the invention compound or salt thereof as a pharmaceutical differs depending on various factors such as symptoms, weight, age or sex of the patient to be administered or administration route.
- the pharmaceutical is used in an amount of 0.1 to 1000 mg/day, preferably 1 to 300 mg/day per adult in terms of the invention compound (1) or salt thereof. It is possible to add the above-described amount once a day or 2 to 4 portions a day.
- Example 9 In a similar manner to Example 9 except for the use of 2-[(ethylthio)(difluoro)methyl]-2-(4-fluorophenyl)oxirane instead of 2-(2,4-difluorophenyl)-2-[(ethylthio)(difluoro)methyl]oxirane, 1-(ethylthio)-1,1-difluoro-2-(4-fluorophenyl)-3-(1 H -1,2,4-triazol-1-yl)-2-propanol was obtained as colorless crystals.
- Example 9 In a similar manner to Example 9 except for the use of 2-[(ethylthio)(difluoro)methyl]-2-(4-trifluoromethylphenyl)oxirane instead of 2-(2,4-difluorophenyl)-2-[(ethylthio)(difluoro)methyl]oxirane, 1-(ethylthio)-1,1-difluoro-2-(4-trifluoromethylphenyl)-3-(1 H -1,2,4-triazol-1-yl)-2-propanol was obtained as colorless crystals.
- Example 15 In a similar manner to Example 15 except for the use of 1-(ethylthio)-1,1-difluoro-2-(4-fluorophenyl)-3-(1 H -1,2,4-triazol-1-yl)-2-propanol instead of 2-(2,4-difluorophenyl)-1-(ethylthio)-1,1-difluoro-3-(1 H -1,2,4-triazol-1-yl)-2-propanol, 1-(ethylsulfonyl)-1,1-difluoro-2-(4-fluorophenyl)-3-(1 H -1,2,4-triazol-1-yl)-2-propanol was obtained as colorless crystals.
- Example 15 In a similar manner to Example 15 except for the use of 1-(ethylthio)-1,1-difluoro-2-(4-trifluoromethylphenyl)-3-(1 H -1,2,4-triazol-1-yl)-2-propanol instead of 2-(2,4-difluorophenyl)-1-(ethylthio)-1,1-difluoro-3-(1 H -1,2,4-triazol-1-yl)-2-propanol, 1-(ethylsulfonyl)-1,1-difluoro-2-(4-trifluoromethylphenyl)-3-(1 H -1,2,4-triazol-1-yl)-2-propanol was obtained as colorless crystals.
- Example 15 In a similar manner to Example 15 except for the use of 2-(2,4-dichlorophenyl)-1-(ethylthio)-1,1-difluoro-3-(1 H -1,2,4-triazol-1-yl)-2-propanol instead of 2-(2,4-difluorophenyl)-1-(ethylthio)-1,1-difluoro-3-(1 H -1,2,4-triazol-1-yl)-2-propanol, 2-(2,4-dichlorophenyl)-1-(ethylsulfonyl)-1,1-difluoro-3-(1 H -1,2,4-triazol-1-yl)-2-propanol was obtained as colorless crystals.
- Example 15 In a similar manner to Example 15 except for the use of 1-[2-(2,4-difluorophenyl)-3-ethylthio-3,3-difluoro-2-methoxypropyl]-1 H -1,2,4-triazole instead of 2-(2,4-difluorophenyl)-1-(ethylthio)-1,1-difluoro-3-(1 H -1,2,4-triazol-1-yl)-2-propanol, 1-[2-(2,4-difluorophenyl)-3-ethylsulfonyl-3,3-difluoro-2-methoxypropyl]-1 H -1,2,4-triazole was obtained as a colorless oil.
- tablets having the above-described composition were prepared.
- the tablets could be formed as sugar coated tablets or film coated tablets.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP35920297 | 1997-12-26 | ||
JP35920297 | 1997-12-26 | ||
JP18619898A JP3638438B2 (ja) | 1997-12-26 | 1998-07-01 | トリアゾール誘導体またはその塩、その製造方法及び当該化合物を有効成分とする医薬 |
JP18619898 | 1998-07-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0927719A1 true EP0927719A1 (fr) | 1999-07-07 |
EP0927719B1 EP0927719B1 (fr) | 2003-07-23 |
Family
ID=26503607
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98123589A Expired - Lifetime EP0927719B1 (fr) | 1997-12-26 | 1998-12-10 | Dérivés de triazole et leurs sels, leurs procédés de préparation et compositions pharmaceutiques les contenant |
Country Status (8)
Country | Link |
---|---|
US (3) | US6083968A (fr) |
EP (1) | EP0927719B1 (fr) |
JP (1) | JP3638438B2 (fr) |
KR (1) | KR100381950B1 (fr) |
CA (1) | CA2256060A1 (fr) |
DE (1) | DE69816580T2 (fr) |
ES (1) | ES2203873T3 (fr) |
TW (1) | TW555751B (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1088827A1 (fr) * | 1999-09-29 | 2001-04-04 | SSP Co., Ltd. | Dérivées d'azoles ou leurs sels |
WO2002087572A1 (fr) * | 2001-04-27 | 2002-11-07 | Nippon Kayaku Kabushiki Kaisha | Preparations de solutions contenant un derive triazole |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3638438B2 (ja) | 1997-12-26 | 2005-04-13 | エスエス製薬株式会社 | トリアゾール誘導体またはその塩、その製造方法及び当該化合物を有効成分とする医薬 |
EP0933368A1 (fr) | 1998-02-02 | 1999-08-04 | SSP Co., Ltd. | Dérivés de triazole ou leurs sels à activité antimycotique,procédé de préparation et et composition pharmaceutique le contenant |
HUP0303249A3 (en) | 2001-02-22 | 2007-03-28 | Sankyo Co | Water-soluble triazole fungicide compounds and pharmaceutical compositions containing them |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0140154A2 (fr) * | 1983-09-26 | 1985-05-08 | Sumitomo Chemical Company, Limited | 1,2,4-Triazolylpropanols, leur préparation et usage |
EP0435081A2 (fr) * | 1989-12-25 | 1991-07-03 | Ss Pharmaceutical Co., Ltd. | Dérivés de triazole |
EP0473387A2 (fr) * | 1990-08-26 | 1992-03-04 | Sankyo Company Limited | Dérivés du triazole antifongiques, leurs préparation et applications |
EP0780380A1 (fr) * | 1995-12-22 | 1997-06-25 | Ss Pharmaceutical Co., Ltd. | Dérivés de triazole à activité antimycotique et intermédiaires |
EP0814079A1 (fr) * | 1996-06-21 | 1997-12-29 | Ss Pharmaceutical Co., Ltd. | Dérivés de triazole ou leurs sels |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BG48681A3 (en) * | 1982-12-14 | 1991-04-15 | Ciba - Geigy Ag | Fungicide means |
US6002028A (en) * | 1995-12-22 | 1999-12-14 | Ss Pharmaceutical Co., Ltd. | Triazole derivative, preparation process thereof and pharmaceutical comprising the same as an effective ingredient |
TW438784B (en) | 1997-08-29 | 2001-06-07 | Ssp Co Ltd | Triazole derivative or salt thereof and pharmaceutical composition for treating mycosis containing the same |
JP3638438B2 (ja) | 1997-12-26 | 2005-04-13 | エスエス製薬株式会社 | トリアゾール誘導体またはその塩、その製造方法及び当該化合物を有効成分とする医薬 |
US5939498A (en) | 1998-04-07 | 1999-08-17 | E. I. Du Pont De Nemours And Company | High modulus polyimide blend |
-
1998
- 1998-07-01 JP JP18619898A patent/JP3638438B2/ja not_active Expired - Fee Related
- 1998-12-09 US US09/207,924 patent/US6083968A/en not_active Expired - Fee Related
- 1998-12-10 DE DE69816580T patent/DE69816580T2/de not_active Expired - Fee Related
- 1998-12-10 EP EP98123589A patent/EP0927719B1/fr not_active Expired - Lifetime
- 1998-12-10 ES ES98123589T patent/ES2203873T3/es not_active Expired - Lifetime
- 1998-12-11 TW TW087120674A patent/TW555751B/zh not_active IP Right Cessation
- 1998-12-15 CA CA002256060A patent/CA2256060A1/fr not_active Abandoned
- 1998-12-22 KR KR10-1998-0057013A patent/KR100381950B1/ko not_active IP Right Cessation
-
2000
- 2000-04-18 US US09/551,567 patent/US6204415B1/en not_active Expired - Fee Related
- 2000-04-18 US US09/551,569 patent/US6194592B1/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0140154A2 (fr) * | 1983-09-26 | 1985-05-08 | Sumitomo Chemical Company, Limited | 1,2,4-Triazolylpropanols, leur préparation et usage |
EP0435081A2 (fr) * | 1989-12-25 | 1991-07-03 | Ss Pharmaceutical Co., Ltd. | Dérivés de triazole |
EP0473387A2 (fr) * | 1990-08-26 | 1992-03-04 | Sankyo Company Limited | Dérivés du triazole antifongiques, leurs préparation et applications |
EP0780380A1 (fr) * | 1995-12-22 | 1997-06-25 | Ss Pharmaceutical Co., Ltd. | Dérivés de triazole à activité antimycotique et intermédiaires |
EP0814079A1 (fr) * | 1996-06-21 | 1997-12-29 | Ss Pharmaceutical Co., Ltd. | Dérivés de triazole ou leurs sels |
Non-Patent Citations (2)
Title |
---|
MIYAUCHI H ET AL: "Structure-activity relationships of sulfur-containing triazole antifungals", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 5, no. 14, 20 July 1995 (1995-07-20), pages 1479-1482, XP004135429 * |
MIYAUCHI H ET AL: "Synthesis and antifungal activities of optically active isomers of SM-8668", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 5, no. 9, 4 May 1995 (1995-05-04), pages 933-936, XP004135523 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1088827A1 (fr) * | 1999-09-29 | 2001-04-04 | SSP Co., Ltd. | Dérivées d'azoles ou leurs sels |
US6528500B1 (en) | 1999-09-29 | 2003-03-04 | Ssp Co., Ltd. | Azole derivatives or salts thereof |
WO2002087572A1 (fr) * | 2001-04-27 | 2002-11-07 | Nippon Kayaku Kabushiki Kaisha | Preparations de solutions contenant un derive triazole |
Also Published As
Publication number | Publication date |
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KR100381950B1 (ko) | 2003-08-25 |
KR19990063296A (ko) | 1999-07-26 |
CA2256060A1 (fr) | 1999-06-26 |
ES2203873T3 (es) | 2004-04-16 |
DE69816580T2 (de) | 2004-02-12 |
JPH11240871A (ja) | 1999-09-07 |
US6194592B1 (en) | 2001-02-27 |
US6083968A (en) | 2000-07-04 |
TW555751B (en) | 2003-10-01 |
JP3638438B2 (ja) | 2005-04-13 |
EP0927719B1 (fr) | 2003-07-23 |
DE69816580D1 (de) | 2003-08-28 |
US6204415B1 (en) | 2001-03-20 |
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